Lessons from Retinoblastoma: Implications for Cancer, Development, Evolution, and Regenerative Medicine

Abstract

Retinoblastoma is a rare childhood cancer of the developing retina, and studies on this orphan disease have led to fundamental discoveries in cancer biology. Retinoblastoma has also emerged as a model for translational research for pediatric solid tumors, which is particularly important as personalized medicine expands in oncology. Research on retinoblastomas has been combined with the exploration of retinal development and retinal degeneration to advance a new model of cell type–specific disease susceptibility termed ‘cellular pliancy’. The concept can even be extended to species-specific regeneration. This review discusses the remarkable path of retinoblastoma research and how it has shaped the most current efforts in basic, translational, and clinical research in oncology and beyond.

Pentoxifylline Enhances the Apoptotic Effect of Carboplatin in Y79 Retinoblastoma Cells

“…In RB cells, it has been observed that involvement of the p53 can mediate cell death (33,34). In the present study, the magnitude and kinetics of the changes in p53 caused by CPt alone were quite different from that caused by PTX alone or by the combined actions of PTX and CPt.…”

RB localizes to DNA double-strand breaks and promotes DNA end resection and homologous recombination through the recruitment of BRG1

“…Germline mutations in the RB1 gene result in retinoblastomas in >90% of the cases, but these patients also show increased incidence of other cancer types, such as osteosarcomas (Dyer 2016). In order to test whether a defect in BRG1 recruitment was also observed in cancer cells with RB1 mutations, we used the I-PpoI system in a widely used osteosarcoma cell line (SAOS-2) that is known for its inactivation of RB.…”

Osteosarcoma: Molecular Pathogenesis and iPSC Modeling

“…RB, caused by autosomal dominant mutations in the RB1 tumor suppressor gene, is a rare cancer of the retina typically found in children with approximately 300 cases in the US and 5–10,000 cases worldwide reported annually [132]. The RB autosomal dominant inheritance pattern suggests that one copy of the RB mutation in each cell is sufficient to increase patient RB risk [132].…”

“…The RB autosomal dominant inheritance pattern suggests that one copy of the RB mutation in each cell is sufficient to increase patient RB risk [132]. Patients with bilateral RB are likely to acquire RB1 germline mutations.…”